Method of administration of a nutritional product to a person having renal failure

ABSTRACT

L-arginine found essential to enhance the glomerular function of the kidneys is used to formulate a low viscosity, calorie-dense, nutritional product for a person having renal failure. In a product free of citric acid or citrates, for oral ingestion, the taste of arginine is counteracted by lactic, malic or adipic acid; in a formulation for tube-feeding, citric acid and citrates in a specified ratio controls the product&#39;s stability. The ratio of calcium to phosphorus is controlled, as is the caloric distribution and water content; the amounts of vitamins and minerals included provide a nutritionally complete formulation.

FIELD OF THE INVENTION

This invention relates generally to a nutritionally complete liquidsupplement (referred to as “product”) for enteral feeding, which hasbeen formulated to address the nutritional needs of persons undergoingrenal dialysis because they suffer from renal failure. The product isformulated for persons who suffer from acute or chronic inflammation ofkidney tissue; in particular, those who have a dysfunctional glomerulus,which is a cluster of capillaries responsible for the production ofurine.

BACKGROUND OF THE INVENTION

It is well established that renal disease affects the nutritional statusof a person with renal failure, both directly and indirectly in so manyways, that it is difficult to achieve a caloric goal by controlling theperson's diet. Major factors which determine the quality of life for apatient are (a) the nutritional status of the patient when dialysis wascommenced; and, (b) the patient's ability to ingest and most efficientlymetabolize the nutrition provided. On the reasonable assumption thatprotein administration may also enhance the rate of recovery from acuterenal failure, U.S. Pat. No. 5,576,287 to Zaloga et al claims a methodfor treating or preventing such failure by feeding the patient meatproteins but fails to teach how elemental arginine, or how much of it,can be added to improve glomerular function; or, how the calcium tophosphorus ratio can be controlled. By “elemental” arginine is meantmolecular arginine (MW=174.2) which is soluble in water. Meat proteinselevate the phosphorus level and there is no indication how the calciumcontent is increased relative to the phosphorus to maintain a Ca/P ratiogreater than 1. Calcium is malabsorbed in patients with renal disease,and they require a relatively high dietary intake; phosphorus is poorlyexcreted, and due to high plasma levels, phosphorus intake must belimited. A ratio greater than 1, on an elemental basis, w/w (weight forweight), helps to optimize the Ca/P balance of a renal patientundergoing dialysis. The '287 composition may also include any othernutrients including amino acids known to have specific renal vasodilatoractions.

Numerous considerations relating to the problems of providing a dietwhich will determine the availability of desirable nutrients arereferred to in U.S. Pat. No. 5,108,767 to Mulchandani and need not bereiterated. Health care professionals dealing with a patient undergoingdialysis must cope with the need to replace the function of the kidneys.They refer to arginine as a non-essential amino acid and do not suggestproviding it in elemental form. Neither the '287 nor the '767disclosures provides the requisite motivation to prepare an acceptablerenal nutritional supplement with elemental L-arginine.

Choosing a renal diet is complicated because specific nutrientrequirements and limitations vary from patients who have acute renalfailure to those who have chronic renal failure or end-stage renaldisease. The choice depends on the stage of renal disease, the type oftreatment prescribed and whether the patient has diabetes (present in upto one half of all renal patients). The challenge is to balance the needto limit the intake of essential nutrients such as phosphorus, potassiumand sodium with the need to provide sufficient protein and energy tomaintain nutritional health.

The primary nutritional need for patients undergoing hemodialysis orperitoneal dialysis is to maintain metabolic homeostasis (normalfunctional indices, positive nitrogen balance, and a stable weight) byfeeding them, either as a sole or supplemental source of nutrition, abalanced nutritional product, when they need a nutritionally completeproduct. Particularly since L-arginine, its precursors and itsmetabolites are deemed to be at the center of the interaction ofdifferent metabolic pathways and interorgan communication (see “Role ofarginine in health and in renal disease” by Reyes, Alvaro A. et al, Am.J. Physiol. 267 F331-F346 1994), and deemed particularly beneficial forglomerular function, the product is fortified with arginine, making itmore available, because free amino acids having molecular weights ofless than about 500 are rapidly absorbed. Other necessary elementalingredients, e.g. minerals, vitamins and protein may be added asdesired, and even additional free amino acids, as long as the followingcritical properties of the final product are met: pH in a slightlyacidic or neutral range e.g. in the range from about 6 to about 8,osmolality below 1000 mOsm/kg water, and viscosity less than 100 cp.

Since a hemodialysis patient averages three treatments per week, or onceevery 56 hours, though the typical patient is not treated after equalintervals, it is essential that the level of arginine in the bloodstreambe maintained. L-arginine is deemed an essential amino acid in patientswith renal failure because of the role it plays in the synthesis ofendothelium-derived relaxing factor, bacterial killing by macrophages,and production of polyamines (see “Amino Acid Profile and Nitric OxidePathway in Patients on Continuous Ambulatory Peritoneal Dialysis:L-Arginine Depletion in Acute Peritonitis” by Heesuk Suh, TatyanaPeresleni, et al Am. Jour. Kidney Diseases, Vol 29, No 5 (1997), pp712-719). Arginine deficiency is suggested as a cause for severalaspects of the uremic syndrome, such as impaired blood pressure control,atherogenesis, vascular smooth muscle cell proliferation, macrophagetoxicity, and impaired antibacterial defense (see “ClinicalNutrition-Enteral and Tube Feeding” by John L. Rombeau and Rolando H.Rolandelli, 3rd edition, pg 448). The maintenance of normal levels ofL-arginine depends on the levels of dietary intake of the amino acid.Though the foregoing indicated the beneficial effect of L-arginine, inview of its well-known unpleasant taste, they offered no suggestion asto how arginine in elemental form might be included in a practical,stable liquid nutritional supplement. The problem is to formulate aproduct with the requisite amount of elemental arginine, yet maintaindesirable viscosity and osmolality; also, to imbue it with a good taste,to find the appropriate order of incorporating the components of therecipe to yield desirable organoleptic properties, and to ensure thatupon sterilization and packaging, the effectiveness of the arginine isnot lost in the product which retains those desirable properties andremains shelf-stable for at least one year.

The composition of this invention is nutritionally complete, by whichterm is meant that the composition contains adequate nutrients tosustain healthy human life for extended periods. The composition can becow milk-based, soy-based, or based on other proteins or nutrients,provided it is fortified with at least enough elemental arginine todouble the contribution of arginine available from a chosen source ofprotein. The caloric density of the nutritionally complete compositionof the invention contains about 2 cal/ml (calories per milliliter) in aready-to-feed form. The liquid, nutritionally complete product flowseasily under gravity, through a conventional feeding tube, and hastolerable osmolality adapted for an adult enteral composition that isintended to come into contact with the gastric contents of the stomach.Though the product is formulated to be tube-fed, it may also beadministered via the normal oral route, and since the latter ispreferred, the product's good taste is an important factor. Thedetrimental effect of bitter elemental arginine on the taste of anyformulation containing more than a trace amount had to be overcome. Thegood taste of the product is provided by the fortuitous effect of one ormore carboxylic acids which also function to neutralize the high pH ofthe arginine. In each formulation, magnesium is provided in the form ofmagnesium carbonate, magnesium sulfate or magnesium oxide, all deemedundesirable in the '767 formulation (col 10, lines 45-50). In a retortedproduct, citric acid is essential in combination with citrates ofsodium, and/or potassium and/or calcium, and the '767 patent teachesthat no citric acid should be used (col 6, lines 43-44).

SUMMARY OF THE INVENTION

L-arginine, which is known to be a non-essential amino acid, is criticalfor enhancing the glomerular function of the kidneys; and, at least asmuch elemental arginine is added in a liquid formulation as is presentin protein incorporated in the liquid, typically contributing at leastabout 0.5% of total calories, and preferably from 0.75% to 7% of totalcalories in the formulation. Because of the combination of a carboxylicacid with elemental arginine, the presterilized liquid formulation has apH in the range from 6 to 8, preferably from 6.5 to 7.5; a viscosityless than 100 cp, preferably 30 to 70 cp; and an osmolality of less thanabout 1000 mOsm/kg water, preferably from about 500 to 900 mOsm/kgwater. Unexpectedly, combining the L-arginine with one or more specificcarboxylic acids not only lowers the pH into the desirable range, butalso imbues the product for oral ingestion with a pleasant taste whichmay be enhanced by other ingredients of the nutritionally completecomposition. In the “oral” formulation, neutralizing the arginine withlactic, adipic or malic acids, which are examples of“arginine-neutralizing acids”, suppresses the bad taste of arginine,lowers the pH and provides a key ingredient which controls viscosity;varying the levels of staple nutrient components within allowable rangeshas surprisingly little effect on the taste, but influences otherproperties substantially. The formulation is stabilized without the useof commonly used protein stabilizers, and is aseptically sterilized at atemperature below 300° F. for from 3 to 10 sec. In the formulation for aretorted product, neutralizing the arginine with a combination of citricacid and citrates (which act as a buffer), in a citric/citrate ratio inthe range from 2 to 8, preferably from 2.5 to 6, both lowers the pH intothe desired range as well as stabilizes the protein so that it surviveshigh temperature sterilization in the range from 250° F. to 270° F. forfrom 10 to 20 min.

This nutritional product is calorie and nutrient-dense, has moderate tohigh protein content, and a high calcium to phosphorus ratio of at least1:1, preferably in the range from about 1:1 to 2:1. The product containsabout 100 g fat/L, about 200 g carbohydrate/L, and essentially no sugarssuch as sucrose, lactose or fructose which have an inordinately highadverse effect on osmolality. If desired, a small amount of fructose,contributing less than 1.5% of total calories, may be added provided thedesired osmolality of the formulation is maintained. In addition, 8 floz of the product which provides about 475 cal, contains from 25 mg to75 mg of magnesium, and 1 liter meets at least 100% of the RDI(reference daily intake) for vitamins and minerals with the exception ofchloride, vitamin D, vitamin A, phosphorus, magnesium, chromium andmolybdenum. Yet, the product meets the nutritional requirements of arenal patient. Specifically the product is low in phosphorus content andcontains L-arginine to help maintain a desirable normal level for eachpatient.

A specific product which provides about 2 cal/ml is characterized byhaving less than 80% by weight water, and the addition of enoughelemental arginine to contribute from about 0.75% to 3% total calories.The balance of arginine may be derived from caseinates. The caloricdistribution for such a product is as follows: from all arginine 1.2% to3%; from protein, 12 to 18%; from fat, 40 to 46%; the balance fromcarbohydrates. In one preferred formulation flavored for oral use,containing essentially no sucrose, lactose or fructose, and lactic acidas taste-suppressant, for those patients who tend to absorbaluminum-containing phosphate binders which are prescribed, no citricacid or citrates are present; in another formulation for tube feeding,containing a combination of citric acid and citrates astaste-suppressant, essentially no lactose, sucrose or fructose ispresent. Citrates are chosen from the salts of sodium, potassium andcalcium to provide a desired balance of the levels of each. Mostpreferably, a citric acid and citrates-containing formulation ispackaged in a retortable container for tube feeding, being hermeticallysealed, sterilized and shelf-stabilized at about 256° F. for 13 min. Anaseptically sterilized container is sterilized at about 280° F. for 4.5sec, for oral or tube feeding a product with no citric acid or citrates.In each product, changing the order of addition of the arginine relativeto the protein and carbohydrates, and that of the oils relative to theforegoing, produces an undesirable product.

BRIEF DESCRIPTION OF THE DRAWING

The invention will best be understood by reference to the followingdetailed description, accompanied with a schematic illustration ofpreferred process steps for making each embodiment of the product:

FIG. 1 is a flow chart for a process to make product free of citric acidor citrates.

FIG. 2 is a flow chart for a process to make product containing bothcitric acid and citrates.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

Dialyzed patients suffering from renal failure over a prolonged periodexperience long-term stress and are at risk for malnutrition. Thecomposition, designed to meet the nutritional needs of humans with renalfailure, contains ingredients such as a protein (amino acid) source, alipid source, and a carbohydrate source. Typically milk, skim milk,casein, hydrolyzed casein, hydrolyzed whey protein, whey, whey proteinconcentrate, vegetable protein concentrate (e.g. soy protein isolate),hydrolyzed vegetable protein (e.g. soy), provide the source of protein,and animal oils, vegetable oils, along with a balanced carbohydrate mixof starch and/or corn syrup solids will supply part or all of the aminoacids and/or protein, lipid, and carbohydrate as well as other nutrientssuch as vitamins and minerals. Sucrose and lactose are excluded becauseof their adverse effect on the osmolality of the product.

One liter of the product preferably comprises from about 3.7 g to 35 garginine, about 70 g to 80 g protein, about 90 g to 110 g fat, about 180g to 220 g carbohydrates and provides about 2000 calories. Mostpreferably, 1 liter of product comprises 74 g protein, 100 g fat, and200 g carbohydrate per liter and from 3.7 g to 12.6 g added elementalL-arginine to contribute in the range from 0.75% to 2.5% of totalcalories respectively.

The water content of the product is less than 80% by weight, preferablyless than 70%. If a patient undergoes peritoneal dialysis every 24 hr,the moisture content may be 80%; but if hemodialysis is performed only 3times a week, the amount of water (when 80% of product is water)ingested in 235.2 fl. oz (4.2 portions, each 8 fl. oz. over 7 days), ismuch greater relative to the water ingested in 235.2 fl. oz containingless than 70% water. This difference is of great significance withrespect to attaining, then maintaining the “dry weight” of the patientbetween dialysis runs. By “dry weight” is meant the actual body weightat normal hydration. In the most preferred embodiment the volume ofwater present is about 65% by weight.

The carbohydrate component of the composition of the invention can beany suitable carbohydrate known in the art to be suitable for use innutritionally complete compositions except added sucrose and lactose.Typical carbohydrates include fructose, xylitol, glucose, maltodextrin,corn syrup, corn syrup solids, rice syrup solids, rice starch, modifiedcorn starch, modified tapioca starch, rice flour, soy flour, and thelike. The adverse effects of the carbohydrate (required to be added) onviscosity and osmolality require that corn syrup or corn syrup solids beused in a major amount relative to any other carbohydrate used. It ismost preferred to use substantially all corn syrup or corn syrup solids.Fiber may be added as part of the carbohydrate.

The fat (lipid) can be any fat known in the art to be suitable for usein nutritionally complete compositions. Typical lipid sources includemilk fat, safflower oil, canola oil, egg yolk lipid, olive oil, cottonseed oil, coconut oil, palm oil, palm kernel oil, soybean oil, sunfloweroil, fish oil and fractions of all above oils derived thereof such aspalm olein, medium chain triglycerides (MCT), and esters of fatty acidswherein the fatty acids are, for example, arachidonic acid, linoleicacid, palmitic acid, stearic acid, docosahexaneoic acid,eicosapentaneoic acid, linolenic acid, oleic acid, lauric acid, capricacid, caprylic acid, caproic acid, and the like. High oleic forms ofvarious oils are also contemplated to be useful herein such as higholeic sunflower oil and high oleic safflower oil. Most preferred is acombination of high oleic sunflower oil, corn oil and MCT oil because itprovides a fat profile which is high in monounsaturated fats, low insaturated fats and the MCT enhances fat absorption.

Preferred protein sources are whey protein, sodium caseinate or calciumcaseinate provided available arginine from the protein is supplementedwith elemental L-arginine in an amount at least as great as that presentin the protein, and preferably from 25% to 600% more than is present inthe protein. The protein source can be any protein and/or amino acidmixture known in the art to be suitable for use in nutritionallycomplete compositions. Typical protein sources are animal protein,vegetable protein such as soy protein, milk protein such as skim milkprotein, whey protein and casein, and amino acids (or salts thereof)such as isoleucine, phenylalanine, leucine, lysine, methionine,threonine, tryptophan, arginine, glutamine, taurine, valine, carnitine,tyrosine, serine, and the like.

Elemental arginine is incorporated by neutralization with a carboxylicacid the choice and amount of which depends upon whether the product isto be sterilized at a temperature above that at which the proteins aredestabilized, typically above 250° F., if not adequately protected. Foraseptic packaging, when the product is to be sterilized at a temperaturein the range from 280° F. to 290 for about 10 sec, the arginine isneutralized with an arginine-neutralizing acid selected from the groupconsisting of lactic acid, malic acid, and adipic acid. The ratio ofarginine-neutralizing acid to arginine is in the range from 0.75 to 1.5for 88% food grade lactic acid. Addition of more than 7% arginine (basedon % of total cal) requires so much arginine-neutralizing acid thattaste of the product is unacceptable. Since lactic acid is amonocarboxylic acid, malic acid is a hydroxydicarboxylic acid and adipicis a dicarboxylic acid, it is only by chance that they exhibit similartaste and stabilization properties. For the retorted product which ishermetically sealed for tube feeding, when the product is to bestabilized at a temperature in the range from about 250° F. to 270° F.for about 15 min, the arginine is neutralized with a combination ofcitric acid and citrates of Na, K and Ca, the ratio of citric acid andcitrates to arginine being in the range from 1 to 2.5. When the ratioexceeds 2.5, or is less than 1, the stability of the protein iscompromised.

Nutritionally complete compositions contain all vitamins and mineralsunderstood to be essential in the daily diet and these should be presentin nutritionally significant amounts. Those skilled in the artappreciate that minimum requirements have been established for certainvitamins and minerals that are known to be necessary for normalphysiological function. Most preferably the product contains therecommended daily allowance (RDA) of nutritional components.

Practitioners also understand that appropriate additional amounts(overages) of vitamin and mineral ingredients need to be provided tocompensate for some loss during processing and storage of suchcompositions. The composition of the invention preferably contains atleast 100% of the RDI in 2000 cal of the product with the exceptionsnoted above.

To select a specific vitamin or mineral compound to be used in thecomposition requires consideration of that vitamin or compound'schemical nature regarding compatibility with the processing chosen andshelf storage.

Examples of minerals, vitamins and other nutrients optionally present inthe formula of the invention include vitamin A, vitamin B₆, vitamin B₁₂,vitamin E, vitamin K, vitamin C, vitamin D, inositol, taurine, folicacid, thiamine, riboflavin, niacin, biotin, pantothenic acid, choline,calcium, phosphorous, iodine, iron, magnesium, copper, zinc, manganese,chloride, potassium, sodium, β-carotene, nucleotides, selenium, andcarnitine. Minerals are usually added in salt form. In addition tocompatibility and stability considerations, the presence and amounts ofspecific minerals and other vitamins will vary somewhat depending on theintended consumer population.

The composition of the invention also typically contains emulsifiersand/or stabilizers such as lecithin, (e.g., egg or soy), carrageenan,xanthan gum, mono- and diglycerides, guar gum, microcrystallinecellulose/carboxymethyl cellulose (“MCC/CMC”), stearoyl lactylates,succinylated monoglycerides, diacetyl tartaric acid esters ofmonoglycerides, polyglycerol esters of fatty acids, or any mixturethereof.

The composition of the invention can be sterilized, if desired, bytechniques known in the art, for example, heat treatment such asautoclaving or retorting, irradiation, and the like, or processed andpackaged either by mild aseptic processing for oral feeding, or by moresevere sterilization for tube-feeding.

The composition of the invention can be packaged in any type ofcontainer known in the art to be useful for storing nutritional productssuch as glass, lined paperboard, plastic, coated metal cans and thelike, but are most preferably packaged in a bottle for tube feeding, andin a paper container for oral use.

The following examples illustrate the invention, but should not beconstrued as limiting the invention which is defined in the appendedclaims.

EXAMPLE 1

Referring to FIG. 1 there is presented a process flow diagram forpreparing the product in an “aseptic system”. In greater detail, an 8000lb batch of product is prepared as follows:

3756.3 lb of deionized water at 140° F. is pumped into a 1000 galprocessing vessel (“processor”) and 6 lb of MCC/CMC (familiarly referredto as “gum”) added. In a separate oil tank is mixed 523.9 lb H.O.sunflower oil, 110.1 lb MCT oil, and 114.2 lb corn oil and the mixtureheated to 100-180° F., preferably 160-165° F. 12.5 lb lecithin is addedto the hot oil (“oil mix”). Add 1.6 lb antifoam to the processor andalso 440 lb sodium caseinate; 128.7 lb calcium caseinate; 50 lbfructose; and 13.1 lb flavor (vanilla). Add 1744 lb corn syrup solidsheated to about 110° F.

In a separate “acid tank” add 20.5 lb lactic acid (commercial 88%) to200 lb deionized water, add 27.2 lb L-arginine and dissolve. Add to theprocessor. Add the oil mix to the processor and flush with 100 lb water.Add 3.4 lb choline chloride and 46.5 lb vitamin/mineral premix-708351with 200 lb water and add to the processor. Flush the acid tank with 200lb water and add the water to the processor. Heat the mixed product to140-180° F., preferably 165° F., in a plate heat exchanger and pump to ade-aerator. Commence homogenizing, and after start of homogenization add150 lb water and 4 lb sodium ascorbate to another tank. Mix to dissolveand add to storage tank. Flush ascorbate tank with 150 lb water. Theproduct is then cooled to a temperature of about 40° F. Agitatecontinuously until a sample indicates an approved product. Asepticallysterilize at 280° F. for 5 sec in Tetra Brik® packages.

The main ingredients (in lb weight) used to make 8000 lb of asepticTetra Brik® product in the above process flow scheme are as follows:deionized water 4756.3; L-arginine 27.2; corn syrup 1744; high oleicsunflower oil 523.9; sodium caseinate 440; calcium caseinate 128.7; cornoil 114.2; MCT oil 110.1; fructose 50; lactic acid 20.5; lecithin 12.5;antifoam 1.6; MCC/CMC (“gum”) 6; flavor 13.1; choline chloride 3.4;vitamin/mineral premix 46.5; sodium ascorbate 4.0.

TABLE 1A The following is a list of ingredients and the relativeamounts, in g/liter, typically served in 1 liter of an illustrativeembodiment of the product for oral feeding, in which total elementalL-arginine provides 1.2% of total calories: g/liter deionized water648.047 36 DE corn syrup 237.56 fructose 6.600 high oleic sunflower oil71.380 sodium caseinate 58.088 calcium caseinate 19.403 MCT oil 15.000corn oil 15.560 L-arginine 3.705 lactic acid 2.787 premix-708351 6.34artificial vanilla flavor 1.790 lecithin 1.703 “gum” 0.812 cholinechloride 0.462 sodium ascorbate 0.545 antifoam 0.218 Total 1090.1

TABLE 1B The following is a list of ingredients in an illustrativeembodiment of the vitamin/mineral premix-708351 (“premix”) and therelative amounts of each: g/liter calcium carbonate 2.425 potassiumchloride 1.583 magnesium carbonate 0.676 tricalcium phosphate 0.347carnitine 0.296 β-carotene 0.223 taurine 0.167 α-tocopheryl acetate0.117 selenium yeast 0.115 biotin 0.080 zinc sulfate 0.070 ferroussulfate 0.061 niacinamide (B3) 0.044 calcium pantothenate 0.028manganese sulfate 0.018 cyanocobalamin B12 0.016 copper gluconate 0.016phytonadione (vitamin K) 0.014 pyridoxine HCl 0.014 folic acid 0.012Vitamin A palmitate 0.007 thiamin HCl (B1) 0.006 potassium iodide 0.006riboflavin (B2) 0.004 cholecalciferol (D) 0.001 Total 6.34

EXAMPLE 2

Referring to FIG. 2 there is presented a process flow diagram forpreparation of the product in a retort system. In greater detail, a10000 lb batch of product is prepared as follows:

4190.7 lb of hot deionized water at above 100° F. and up to 180° F. ispumped into a 1000 gal processor and 2.0 lb antifoam added along with7.5 lb “gum”. Add 33.7 lb citrates, 13.7 lb citric acid and 44.2 lbL-arginine to the processor and agitate on high for about 10 minutes.Then add 532.9 lb sodium caseinate, 178 lb calcium caseinate, 1900 lbcorn syrup solids, and 60.6 lb fructose. Flush lines with DI water, addto the processor and heat to a temperature below 165° F., preferably inthe range from 150-160° F. In a first oil slurry tank, mix 137.6 lb MCToil, 142.8 lb corn oil and 200 lb high oleic sunflower oil and commenceheating. When the oil reaches 140-180° F., preferably 160-165° F., add15.6 lb soy lecithin. In a second oil slurry tank pour 454.9 lb higholeic sunflower oil and heat to 140-180° F., preferably 160-165° F. Addthe contents of the two oil slurry tanks to the processor and maintainthe temperature of its contents in the range 130-180° F., preferably atabout 165° F. Add 300 lb DI water and 81.7 lb of vitamin/mineral premix280-23. In a 10 gal vessel containing 50 lb DI water at room temperaturemix 4.2 lb choline chloride. Add to the dissolved premix-280-23, and addto the processor. Homogenize the mixture through a two-stagehomogenizer, cool and store the cooled homogenized product in a storagetank. If desired, the mixture may be homogenized a second time. Add 5.0lb ascorbate and agitate to disperse.

The homogenized product is packaged, preferably in 1 liter plasticbottles. The bottles are preferably sterilized by immersing the bottlesin water at 250° F. and agitating them end-over-end for about 19 min.

The main ingredients (in lb weight) used to make 10000 lb of a specificembodiment of the product for tube feeding in the above process flowscheme are as follows: deionized water 6190.7; L-arginine 44.2; cornsyrup solids 1900; high oleic sunflower oil 654.9; sodium caseinate532.9; calcium caseinate 178; corn oil 142.8; MCT oil 137.6; fructose60.6; citric acid 13.7; citrates 33.7; soy lecithin 15.6; antifoam 2.0;“gum” 7.5; choline chloride 4.2; vitamin/mineral premix-280-23 81.7;and, sodium ascorbate 5.0.

TABLE 2A The following is a list of ingredients and the relative amountsof each, in a first illustrative embodiment of the product for tubefeeding in which total elemental L-arginine provides about 1.2% of totalcalories: g/liter deionized water 674.787 corn syrup solids 206.550 higholeic sunflower oil 71.380 sodium caseinate 58.088 calcium caseinate19.403 MCT oi1 15.000 corn oil 15.560 L-arginine 4.816 premix-280-238.900 fructose 6.600 sodium citrate 2.882 lecithin 1.703 citric acid1.495 “gum” 0.812 potassium citrate 0.800 choline chloride 0.462 sodiumascorbate 0.545 antifoam 0.218 Total 1090.00

TABLE 2B The following is a list of ingredients in an illustrativeembodiment of the vitamin/mineral premix-280-23 and the relative amountsof each: g/liter calcium citrate 4.445 potassium chloride 1.642magnesium sulfate 0.755 tricalcium phosphate 0.346 carnitine 0.307β-carotene 0.223 magnesium oxide 0.200 maltodextrin 0.180 taurine 0.167α-tocopherylacetate 0.117 selenium yeast 0.115 biotin 0.080 zinc sulfate0.070 ferrous sulfate 0.061 niacinamide (B3) 0.043 calcium pantothenate0.027 magnesium sulfate 0.018 cyanocobalamin B12 0.016 copper gluconate0.016 phytonadione (vitamin K) 0.014 pyridoxine HCl 0.014 folic acid0.012 Vitamin A palmitate 0.007 thiamin HCl (B1) 0.006 potassium iodide0.006 riboflavin (B2) 0.004 cholecalciferol (D) 0.001 Total 8.90

TABLE 2C The following is a list of ingredients and the relative amountsof each, in a second illustrative embodiment of the product for tubefeeding in which total elemental L-arginine provides about 1% of totalcalories: g/liter deionized water 645.480 liquid corn syrup 238.408fructose 6.600 high oleic sunflower oil 71.380 sodium caseinate 58.088calcium caseinate 19.403 MCT oil 15.000 corn oil 15.560 L-arginine 3.705premix 267-129 3.010 calcium citrate 4.445 potassium chloride 1.642lecithin 1.703 choline chloride 0.462 sodium ascorbate 0.273 antifoam0.218 “gum” 0.812 citric acid 1.150 β-carotene 0.223 sodium citrate2.482 Total 1090.05

TABLE 2D The following is a list of ingredients and the relative amountsof each, in a third illustrative embodiment of the product for tubefeeding in which total elemental L-arginine provides about 2% of totalcalories: g/liter deionized water 645.850 liquid corn syrup 238.408fructose 6.600 high oleic sunflower oil 71.380 sodium caseinate 54.900calcium caseinate 18.523 MCT oil 15.000 corn oil 15.560 L-arginine 7.410premix 267-129 3.010 calcium citrate 4.445 potassium chloride 1.642lecithin 1.703 choline chloride 0.462 sodium ascorbate 0.273 antifoam0.218 “gum” 0.812 citric acid 2.300 β-carotene 0.223 sodium citrate1.282 Total 1090.00

TABLE 2E The following is a list of ingredients and the relative amountsof each, in a fourth illustrative embodiment of the product for tubefeeding in which total elemental L-arginine provides about 3% of totalcalories: g/liter deionized water 648.430 liquid corn syrup 236.915fructose 6.600 high oleic sunflower oil 71.380 sodium caseinate 50.819calcium caseinate 16.980 MCT oil 15.000 corn oil 15.560 L-arginine12.602 premix 267-129 3.010 calcium citrate 4.445 potassium chloride1.642 lecithin 1.703 choline chloride 0.462 sodium ascorbate 0.273antifoam 0.218 “gum” 0.812 citric acid 2.930 β-carotene 0.223 Total1090.01

TABLE 2F The following is a list of ingredients in an illustrativeembodiment of the vitamin/mineral premix 267-129 and the relativeamounts of each: g/liter magnesium sulfate 1.511 tricalcium phosphate0.346 carnitine 0.307 taurine 0.167 α-tocopherylacetate 0.117 seleniumyeast 0.115 biotin 0.080 zinc sulfate 0.070 ferrous sulfate 0.061maltodextrin 0.047 niacinamide (B3) 0.044 calcium pantothenate 0.027manganese sulfate 0.018 cyanocobalamin B12 0.016 copper gluconate 0.016phytonadione (vitamin K) 0.014 pyridoxine HCl 0.014 folic acid 0.012Vitamin A palmitate 0.007 thiamin HCl (B1) 0.006 potassium iodide 0.006riboflavin (B2) 0.004 cholecalciferol (D) 0.001 Total 3.01

In the foregoing examples, a very small amount of fructose is used forflavor, despite its adverse effect on osmolality. Substitutingmaltodextrin would relieve the problem with excess osmolality. To theextent that the addition of sucrose or lactose can be tolerated fortheir adverse effect on osmolality, small amounts of either may be used,but less than the amount of fructose used in the foregoing examples.

We claim:
 1. A method of treating a patient suffering from renal failurecomprising administering to said patient a composition comprisingL-arginine, an arginine-neutralizing acid, protein, fat, carbohydrates,vitamins and minerals, wherein the arginine-neutralizing acid isselected from the group consisting of lactic acid, malic acid, adipicacid, and mixtures thereof, and wherein the composition has a pH of from6 to 8, an osmolality of less than 1000 mOsm/kg water, and a viscosityof less than 100 centipoise as determined by a Brookfield viscometerusing spindle #1 at 60 rpm.
 2. The method according to claim 1 whereinthe composition has a pH of from 6.5 to 7.5.
 3. The method according toclaim 1 wherein the composition has a caloric density of about 2 cal/ml.4. The method according to claim 3 wherein the L-arginine contributesfrom about 0.5% to 7% of total calories.
 5. The method according toclaim 4 wherein the L-arginine contributes from about 1.2% to 3% oftotal calories.
 6. The method according to claim 1 wherein the water ispresent in an amount less than 75% by weight.
 7. The method according toclaim 1 wherein the osmolality of the composition is from about 500 toabout 900 mOsm/kg water.